Contraction Of Uterine Smooth Muscle Research Articles

Erratum to: Tianeptine’s effects on spontaneous and Ca2+-induced uterine smooth muscle contraction

Erratum to: Tianeptine’s effects on spontaneous and Ca²⁺-induced uterine smooth muscle contraction

Tianeptine’s effects on spontaneous and Ca2+-induced uterine smooth muscle contraction

Tianeptine is a novel anti-depressant with an efficacy equivalent to that of classical anti-depressants. Additional beneficial effects include neuroprotection, anti-stress and anti-ulcer properties whose molecular mechanisms are still not completely understood but may involve changes in the anti-oxidant defence system. Herein, we have studied the effects of tianeptine on both contractile activity of isolated rat uteri and components of the endogenous anti-oxidative defence system. Tianeptine-induced dose-dependent inhibition of both spontaneous and Ca2+-induced contraction of uterine smooth muscle. The effect was more pronounced in the latter. Tianeptine treatment increased glutathione peroxidase (GSH-Px) and catalase (CAT) activities in spontaneous and Ca2+-stimulated uteri. A significant decrease in glutathione-reductase (GR) activity in both spontaneous and Ca2+-induced uterine contractions after tianeptine treatment indicated a reduction in reduced glutathione and consequently a shift toward a more oxidised state in the treated uteri. In spontaneously contracting uteri, tianeptine caused a decrease in copper-zinc SOD (CuZnSOD) activity. Tianeptine's anti-depressant effects may be accomplished by triggering a cascade of cellular adaptations including inhibition of smooth muscle contractility and an adequate anti-oxidative protection response.

Shakuyaku‐kanzo‐to inhibits smooth muscle contractions of human pregnant uterine tissue in vitro

Shakuyaku-kanzo-to (SK) is a herbal medicine and is known to possess an antispasmodic effect on skeletal muscle and intestinal smooth muscle. However, it is unclear whether SK is effective in antagonizing uterine smooth muscle contractions. Herein, we investigated the effects of SK on smooth muscle contractions of human pregnant uterine samples. We prepared myometrial strips from uterine tissues of pregnant women who underwent cesarean section for obstetrical indications, and examined the inhibitory effects of SK and its components, shakuyaku (S) and kanzo (K), on agonist-induced and spontaneous contractions in vitro. Oxytocin, prostaglandinF(2α) , and high KCl were utilized as agonists in this study. SK inhibited agonist-induced and spontaneous contractions in a dose-dependent manner. Inhibition of SK on oxytocin-induced contractions occurred at a concentration of 100 µg/mL and reached maximum effect at a concentration of more than 1000 µg/mL. The half max inhibitory concentration of SK was approximately 440 µg/mL in oxytocin-induced contractions. SK at 1000 µg/mL completely inhibited the oxytocin- and prostaglandinF(2α)-induced contractions but not the high KCl-induced contractions. The inhibitory effects on agonist-induced contractions of K, but not S, matched those of SK. These results suggest that the inhibitory effect of SK on smooth muscle contractions is due to K. The mechanism of the inhibitory effects of SK on oxytocin- and prostaglandinF(2α) -induced contractions may differ from that on KCl-induced contractions.

Relaxant effect induced by wogonin from Scutellaria baicalensis on rat isolated uterine smooth muscle

Context: Wogonin is a flavone derivative isolated from Scutellaria baicalensis Georgi (Labiatae) root, which is a traditional Chinese drug used as an anti-inflammatory and for management of dysmenorrhea.Objective: The effect of wogonin on the uterus has not yet been examined. We investigated the relaxant effects of wogonin on contractile activity of isolated uterine strips of rats.Materials and methods: The effect of wogonin on spontaneous uterine contraction, and uterine contraction induced by agonists, K+-depolarization and oxytocin in Ca2+-free solution was observed. To clarify the type of potassium channel, we tested the effects of 4-aminopyridine, tetraethylammonium and glibenclamide.Results: Wogonin reduced the contractile amplitude of uterine strip smooth muscle of rats in a dose-dependent manner. The concentration of wogonin for reducing the contraction amplitude by 50% (IC50) on spontaneous contractions was 60.5 μM. Wogonin also inhibited the contraction induced by three agonists (oxytocin, prostaglandin F2α and acetylcholine). For the uterine strips pretreated with oxytocin in Ca2+-free solution or K+-depolarization, wogonin showed relaxant effect on the induced uterine contractions. In addition, whereas the inhibitive effect of wogonin on the contraction of uterine smooth muscle in rats could be partly blocked by 4-aminopyridine and tetraethylammonium, it was not influenced by glibenclamide.Discussion and conclusion: Wogonin significantly inhibited the contraction of rat uterine smooth muscle probably through the inhibition of the inflow of extracellular calcium into cells via cell membrane, and intracellular release of calcium ions. In addition, the relaxant effect induced by wogonin might be due in part to the opening of voltage-dependent and large conductance Ca2+-activated K+ channels.

Smooth Muscle Pharmacology in the Isolated Virgin and Pregnant Rat Uterus and Cervix

Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle α-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 ± 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2α, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The β-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ∼10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ∼20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during pregnancy.

Prostaglandins and its analogues : An approach for treatment of anoestrus and to enhance breeding efficiency

Cloprostenol is a synthetic prostaglandin F analogue. It is a FP (Prostaglandin F) receptor agonist, which shows 2· powerful luteolytic effects. It also stimulates the contraction of uterine and bronchial smooth muscle and produces vasoconstriction in some vessels. Anoestrous may be due to some conditions like abnormal pregnancy, early pregnancy, pyometra, endometritis, retention of placenta, maceration and mummification. So, get rid of this conditions cloprostenol is widely used. It has been now in vogue to administer PGF or its analogue in early 2· postpartum cows and buffaloes in order to hasten early resumption of cyclic ovarian activity and thereby to increase the reproductive efficiency. To improve reproductive efficiency, it is necessary to inseminate cows early in the breeding season so that, thereby achieving a more compact calving season. Breeding efficiency is increased by means of synchronization of estrus, conception rate and pregnancy rate. Estrus synchronization can be achieved by lysis of corpus luteum by administration of prostaglandin (PGF ) or its synthetic analogue on 5-17 2· days of the estrus cycle. The cows will return to estrus within 3-5 days. The effective therapeutic doses for cloprostenol are 500 µg in cattle and 175 µg in pigs. However, for R-cloprostenol, the recommended doses are: 150 µg in cattle and 75 µg in pigs. In both cases, it is administered by the intramuscular route.

A Modified Hai–Murphy Model of Uterine Smooth Muscle Contraction

We extend and analyze the Wang and Politi modified Hai-Murphy model of smooth muscle cell contractions to capture uterine muscle cell response to variations in intracellular calcium concentrations. This model is used to estimate values of unknown parameters in uterine smooth muscle cell cross-bridging. Uterine motility is responsible for carrying out important processes throughout all phases of the nonpregnant female reproductive cycle, including sperm transport, menstruation, and embryo implantation. The modified Hai-Murphy partial differential equation model accounts for the displacement of myosin cross-bridge heads relative to their binding sites. This model was originally developed for the study of airway contractions; we now extended it for use in modeling nonisometric uterine contractions. Our extended model incorporates cross-bridge position and contractile velocity into the original model, resulting in more accurate modeling of the initial stages of contraction and modeling nonisometric contractions. Numerical simulations show that the contraction rate in our extended model is faster than the original Hai-Murphy model. These simulations provide quantitative estimates for the increased level of responsiveness of our extended model to intracellular calcium concentrations. The extended model and new parameter estimates for the cross-bridging can be coupled with uterine flow models to advance our understanding of embryonic motility and intrauterine flow.

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

Rates of premature birth are alarming and threaten societies and healthcare systems worldwide. Premature labor results in premature birth in over 50% of cases. Preterm birth accounts for three-quarters of infant morbidity and mortality. Children that survive birth before 34 weeks gestation often face life-long disability. Current treatments for preterm labor are wanting. No treatment has been found to be generally effective and none are systematically evaluated beyond 48 h. New approaches to the treatment of preterm labor are desperately needed. Recent studies from our laboratory suggest that the uterine muscle is a unique compartment with regulation of uterine relaxation unlike that of other smooth muscles. Here we discuss recent evidence that the mechanically activated 2-pore potassium channel, TREK-1, may contribute to contraction-relaxation signaling in uterine smooth muscle and that TREK-1 gene variants associated with human labor and preterm labor may lead to a better understanding of preterm labor and its possible prevention.

Effects of Resveratrol, a Grape Polyphenol, on Uterine Contraction and Ca2+Mobilization in Ratsin Vivoandin Vitro

Dysmenorrhea is directly related to elevate prostaglandin F (PGF)(₂α) levels. In Western medicine, this condition is treated using nonsteroidal antiinflammatory drugs. Because nonsteroidal antiinflammatory drugs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative for treating dysmenorrhea. Many special physiological components used in Chinese medicine, such as resveratrol, have been isolated and identified. Resveratrol has many physiological functions, such as antioxidation and anticarcinogenic effects. However, the relationship between uterine smooth muscle contraction and resveratrol remains unknown. Here, we studied the in vitro and in vivo effects of resveratrol on uterine smooth muscle contraction. The uterus was separated from a female Sprague Dawley rat, and uterine smooth muscle contraction activity was measured and recorded. The results demonstrated that 1) resveratrol treatment inhibited PGF(₂α)-, oxytocin-, acetylcholine-, and carbachol-induced uterine contractions in rats; 2) resveratrol inhibited uterine contractions stimulated by the Ca²(+) channel activator (Bay K 8644) and depolarization in response to high K(+) (KCl); 3) resveratrol inhibited PGF(₂α)-induced increases in the [Ca²(+)]i in human uterine smooth muscle cells; 4) resveratrol could mimic Ca²(+) channel blockers to block Ca²(+) influx through voltage-operated Ca²(+) channels in the plasma membrane; and 5) resveratrol inhibited PGF(₂α)-induced uterine contractions in rats in vivo. Resveratrol inhibited uterine contractions induced by PGF(₂α) and high K(+) in a concentration-dependent manner in vitro; furthermore, it inhibited Ca²(+)-dependent uterine contractions. Thus, resveratrol consistently suppressed the increases in intracellular Ca²(+) concentrations ([Ca²(+)]i) induced by PGF(₂α) and high K(+) concentrations. It can be assumed that resveratrol probably inhibited uterine contraction by blocking external Ca²(+) influx, leading to decreased [Ca²(+)]i. Therefore, resveratrol can be considered as a feasible alternative therapeutic agent for dysmenorrhea.

Assessment of biological activity of novel peptide analogues of angiotensin IV

Angiotensin IV (Ang IV) is a metabolite of angiotensin II which acts on specific AT(4) receptors identified as the enzyme insulin regulated aminopeptidase (IRAP). The transduction process of these receptors is unresolved, but Ang IV inhibits the aminopeptidase activity. Ang IV improves cognition in animal models thus there is a desire to develop metabolically stable analogues for further development. Peptide analogues of Ang IV were obtained commercially or synthesised. Each peptide was tested in vitro for its ability to inhibit the aminopeptidase activity (IRAP) of mouse brain homogenates and for its effects on isolated rat uterine smooth muscle. [Des-Val(1) ]-Ang IV, acetylated-Ang IV-amide, Ang IV-amide and [des-His(4) ]-Ang IV all inhibited IRAP. [Sar(1) , Ile(8) ]-Angiotensin II (10 µm) had an effect greater than that of Ang IV or any of the other analogues studied. In isolated uterine smooth muscle, angiotensins II and IV induced contractions, which could be antagonised by an AT(1) -receptor antagonist. None of the novel peptides induced uterine smooth muscle contractions, but [Sar(1) , des Arg(2) -Gly(8) ]-angiotensin II showed significant antagonism of the contractile effects of angiotensin II and carboxyamide-terminated Ang IV-NH(2) showed antagonism of Ang IV-induced contractions. This study provides five novel inhibitors of IRAP worthy of assessment in behavioural models of learning and memory. The analogues are devoid of AT(1) receptor agonist properties, and the carboxyamide analogue presents an opportunity to elucidate the mechanism of action of Ang IV as, like Ang IV, it inhibits IRAP, but antagonises the effects of Ang IV on isolated smooth muscle.

The In Vitro Study of Resveratrol on Uterine Contraction and Ca2+ Mobilization in the Rat.

Dysmenorrhea is directly related to elevated PGF2alpha levels. It is treated with NSAIDs (nonsteroid antiinflammatory drugs) in Western medicine. Since NSAIDs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative medicine. Many special physiological components (ex: Resveratrol) in Chinese medicine have been isolated and identified. Resveratrol have a lot of physiological functions like anti-oxidation and anti-cancer effects. However, the relationship between uterine smooth muscle contraction and resveratrol remains veiled. We studied the in vitro effects of resveratrol on uterine smooth muscle contraction. The uterus was separated from female SD rat and uterine smooth muscle contraction activity was measured and recorded. Resveratrol inhibited uterine contractions induced by PGF2alpha, Ca2+ channel activator Bay K 8644, and high K+ in a concentration-dependent manner in vitro; furthermore, resveratrol inhibited the Ca2+-dependent uterine contractions. Thus, resveratrol consistently suppressed the increases in intracellular Ca2+ concentrations ([Ca2+]i) induced by PGF2alpha and high K+. Thus, resveratrol probably inhibited uterine contraction by blocking external Ca2+ influx, leading to a decrease in [Ca2+]i. Thus, resveratrol may be considered as a feasible alternative therapeutic agent for dysmenorrhea. (poster)

A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

Conventionally, G protein-coupled receptors are thought to increase calcium via inositol 1,4,5-trisphosphate (InsP(3)). More recent evidence shows that an alternative second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), also has a role to play, causing researchers to question established calcium releasing pathways. With the recent development, by our group, of cell-permeant NAADP (NAADP-aceteoxymethyl ester) and a selective NAADP receptor antagonist (Ned-19; 1-(3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid),the ability to investigate this signaling pathway has improved. Therefore, we investigated a role for NAADP in oxytocin-mediated responses in the rat uterus. Oxytocin- and NAADP-mediated effects were investigated by using contractile measurements of whole uterine strips from rat in organ baths. Responses were correlated to calcium release in cultured rat uterine smooth muscle cells measured by fluorescence microscopy. Inhibition of both oxytocin-induced contraction and calcium release by the traditional NAADP-signaling disrupter bafilomycin and the NAADP receptor antagonist Ned-19 clearly demonstrated a role for NAADP in oxytocin-induced signaling. A cell-permeant form of NAADP was able to produce both uterine contractions and calcium release. This response was unaffected by depletion of sarcoplasmic reticulum stores with thapsigargin, but was abolished by both bafilomycin and Ned-19. Crucially, oxytocin stimulated an increase in NAADP in rat uterine tissue. The present study demonstrates directly that NAADP signaling plays a role in rat uterine contractions. Moreover, investigation of this signaling pathway highlights yet another component of oxytocin-mediated signaling, stressing the need to consider the action of new components as they are discovered, even in signaling pathways that are thought to be well established.

693: Increased expression of transient receptor vanilloid channels during pregnancy regulates uterine smooth muscle cell calcium entry and contraction

693: Increased expression of transient receptor vanilloid channels during pregnancy regulates uterine smooth muscle cell calcium entry and contraction

The effects of etomidate on the contraction of pregnant rat uterine smooth muscle.

It has been reported that etomidate has the relaxant effects on vascular, tracheal, and non-pregnant uterine smooth muscle in vitro. The purpose of this study was to investigate the relaxant effects of etomidate on the contraction of the pregnant rat uterine smooth muscle. Uterine muscle tissues were obtained from pregnant rats (n = 15). The uterine segments were mounted in organ baths filled with Krebs solution. After oxytocin-induced contractile activity had been established, etomidate in incremental concentrations (10(-7) to 10(-3) M) was added cumulatively to the bath, each administered 20 min apart, and resultant changes in contractile activity were continuously recorded. EC5 (effective concentration of 5% reduction), EC25, EC50, EC75, and EC95 on active tension were calculated using a probit model. Etomidate (10(-7) to 10(-3) M) induced dose-dependent decreases in amplitude and frequency of uterine contraction. The EC50 of etomidate on active tension were 5.91 x 10(-5) M. These results demonstrate that etomidate had inhibitory effects on pregnant rat uterine muscle at supraclinical concentration (5.91 x 10(-5) M).

Role of T-type Ca2+ Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle

Although extracellular Ca(2+) entry through the voltage-dependent Ca(2+) channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type Ca(2+) channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type Ca(2+) channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and [Ca(2+)](i) were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18~20 of gestation: term=22 days). The expression of T-type Ca(2+) channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (<1 microM) of nifedipine, a L-type Ca(2+) channel blocker, produced a decrease in the amplitude of the spontaneous Ca(2+) transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (alpha1G, alpha1H) of the T-type Ca(2+) channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous Ca(2+) transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous Ca(2+) transients consistent with the reduction of the frequency. It is concluded that T-type Ca(2+) channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.

Role of Oxytocin/Oxytocin Receptor System in Regulation of Cell Growth and Neoplastic Processes

Novel sites of oxytocin receptor expression have recently been detected in central nervous system, cardiomyocytes, endothelial cells, various carcinoma cells, etc. These and other discoveries have greatly expanded the classical biological roles of oxytocin, which are stimulation of uterine smooth muscle contraction at parturition and milk ejection during lactation. It is becoming clear that the great diversity of oxytocin actions in the brain and peripheral organs is paralleled by activation of a diversity of signalling pathways. On the other hand, until now only one single oxytocin receptor type has been detected. This receptor belongs to G protein-coupled receptors and in dependence on cell conditions it binds to different G proteins; this phenomenon is called receptor-G protein promiscuity. Thus, in the same cells oxytocin can activate multiple responses at the same time. Recently, the oxytocinergic system has also been implicated in the growth modulation of various neoplastic cells, where it may inhibit or stimulate cell proliferation in dependence on cell type and activated metabolic pathways. The discovery of novel oxytocin receptor-linked signalling cascades brings interesting knowledge opening new avenues for research in oncology and molecular pharmacology with perspectives of finding new therapeutic agents.

Characterization of Serotonin Receptors in Pregnant Human Myometrium

The monoamine, 5-hydroxytryptamine (5-HT), stimulates contraction of human uterine smooth muscle (myometrium), but the receptor subtypes involved have not been characterized. We studied the effects of a range of 5-HT receptor subtype-selective agonists and antagonists in isolated strips of myometrium obtained at the time of caesarean section. The 5-HT(1A) receptor agonist, 8-hydroxy-2-dipropylaminotetralin, produced an increase in contractions that was highly variable, of low potency, and was not significantly inhibited by the 5-HT(1A) antagonist WAY100635 [[O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide]. The 5-HT(2) receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT), produced a strong, consistent, and concentration-dependent stimulation of contractions (pEC(50) = 7.60 +/- 0.10, n = 5). The 5-HT(2A) receptor antagonist, ketanserin [3-[2-[4-(4-fluoro benzoyl)-piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione], caused a parallel shift in the response to alpha-Me-5-HT, with a pK(B) value consistent with its known affinity for the 5-HT(2A) receptor (pK(B) = 8.47 +/- 0.16, n = 5), but it had no effect on the response to oxytocin. The 5-HT(2B) and 5-HT(2C) receptor agonists, BW723C86 [(alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine)] and Ro-60-01-75 [(S)-2-(6-chloro-5-fluoro-indol-1-yl)-1-methyl-ethylamine fumarate], produced inconsistent responses at potencies that were lower than expected for activation of their cognate receptors. The response to alpha-Me-5-HT was unaffected by the 5-HT(2B) and 5-HT(2C) receptor antagonists, SB204741 [(N-(1-methyl-1H-indolyl-5-yl)-N-(3-methyl-5-isothiazolyl)urea)] and RS102221 [8-[5-(2,4-dimethoxy-5-(4-trifluoromethyl phenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione]. The 5-HT(1B/1D) receptor agonist, sumatriptan [1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide], the 5-HT(4) agonist, cisapride [4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidyl]-2-methoxy-benzamide], and the 5-HT(7) agonist, AS19 [(2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin], all had no effect on myometrial contractility. 5-HT(2A) receptor mRNA and immunoreactivity were identified using reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. Specific binding of [(3)H]ketanserin was demonstrated. This study provides strong evidence for the expression of contractile 5-HT(2A) receptors in pregnant human myometrium, and this receptor is a potential target for novel uterotonic therapies.

X-ray and high-resolution 1H and 13C NMR of smooth muscle relaxant sesquiterpene lactones

The structure and stereochemistry of four sesquiterpene lactones, budlein A (1), zaluzanin A (2), and glaucolides D (3a) and E (3b), isolated from Mexican Asteraceae species, for which only partial NMR data could be found in the literature, were determined. A combination of 1D and 2D high-resolution NMR experiments, such as DEPT, COSY, NOESY, ROESY, HMQC, HSQC, and HMBC, were used to completely assign the 1H and 13C spectra. The crystal structures of zaluzanin A (2) and glaucolide E (3b) were also determined. Glaucolides D and E have been previously reported to relax KCl-induced contraction in rat uterine smooth muscle; therefore, the effects of zaluzanin A and budlein A were examined in the same model. It was found that both compounds can relax contraction induced by KCl, but only zaluzanin A induced relaxation when contraction was induced with oxytocin. The preliminary biological test results according to these profiles are reported in this paper.Key words: NMR data, X-ray data, sesquiterpene lactones, Mexican Asteraceae, smooth muscle relaxant.

Emerging tocolytics: challenges in designing and testing drugs to delay preterm delivery and prolong pregnancy

The global rate of preterm delivery (before 37 completed weeks of pregnancy) is increasing and there are no effective means available to prevent this rise. Prematurity is the principal cause of neonatal mortality and a major cause of pediatric morbidity and long-term disability. Current strategies to prolong pregnancy are based on inhibiting the mechanisms that effect uterine smooth muscle (myometrium) contractions in women who are in preterm labor. Most drugs in this group were developed for other purposes. Newer strategies are designed to maintain a state of uterine quiescence and pregnancy, preventing the myometrium from initiating contractions and entering preterm labor. Again, it may be possible to use existing drugs for pregnancy maintenance. Several financial and practical barriers exist for developing completely new drugs to delay labor. Designing clinical trials to test tocolytics is complicated, as the health of two patients must be considered and the nature of preterm birth and its outcomes are different at early preterm labor (< 28 weeks) and late preterm labor (34 – 36 weeks).

Effects of adlay hull extracts on uterine contraction and Ca2+mobilization in the rat

Dysmenorrhea is directly related to elevated PGF(2alpha) levels. It is treated with nonsteroid antiinflammatory drugs (NSAIDs) in Western medicine. Since NSAIDs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative medicine. Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for treating dysmenorrhea. However, the relationship between smooth muscle contraction and adlay extracts remains veiled. Therefore, we investigated this relationship in the rat uterus by measuring uterine contraction activity and recording the intrauterine pressure. We studied the in vivo and in vitro effects of the methanolic extracts of adlay hull (AHM) on uterine smooth muscle contraction. The extracts were fractionated using four different solvents: water, 1-butanol, ethyl acetate, and n-hexane; the four respective fractions were AHM-Wa, AHM-Bu, AHM-EA, and AHM-Hex. AHM-EA and its subfractions (175 microg/ml) inhibited uterine contractions induced by PGF(2alpha), the Ca(2+) channel activator Bay K 8644, and high K(+) in a concentration-dependent manner in vitro. AHM-EA also inhibited PGF(2alpha)-induced uterine contractions in vivo; furthermore, 375 microg/ml of AHM-EA inhibited the Ca(2+)-dependent uterine contractions. Thus 375 microg/ml of AHM-EA consistently suppressed the increases in intracellular Ca(2+) concentrations induced by PGF(2alpha) and high K(+). We also demonstrated that naringenin and quercetin are the major pure chemical components of AHM-EA that inhibit PGF(2alpha)-induced uterine contractions. Thus AHM-EA probably inhibited uterine contraction by blocking external Ca(2+) influx, leading to a decrease in intracellular Ca(2+) concentration. Thus adlay hull may be considered as a feasible alternative therapeutic agent for dysmenorrhea.